The usual treatment of heroin addiction in Russia involves detoxification and 2-4 weeks of rehabilitation with referral to outpatient follow-up. Though most patients complete inpatient treatment, few keep follow-up appointments and relapse rates are high. More effective therapies are needed, especially in view of the epidemic of heroin addiction that has resulted in the spread of HIV and other infectious diseases. A recently completed study of 52 patients randomized to oral naltrexone (ON) or oral naltrexone placebo (ONP) has shown efficacy in preventing relapse and reducing HIV risk but dropout was a problem with only 44% of ON patients proven to have not relapsed by 6 months as compared to 16% of ONP patients. A larger study of 280 patients randomized to ON or ONP with or without fluoxetine will further evaluate these early results and determine if adding a SSRI improves outcome. Recruitment into this study is almost completed but is not finished and outcome data are not yet available. We think that retention and outcome can be also improved by depot injectable naltrexone (DIN), and in this study we propose to compare ON with DIN. DIN is not approved for use in Russia and we would like the results of this study to be acceptable to Russian authorities that might approve it for general use. Thus we propose a placebo-controlled, double-blind/double-dummy design since a placebo-controlled trial is required by the Russian equivalent of our FDA as a condition for approval of a pharmacotherapy. Participants will be male and female heroin addicts who have been detoxified in addiction treatment hospitals in St. Petersburg and have a family member willing and able to supervise medication compliance and facilitate follow-up. After giving informed consent and confirming the absence of physiologic dependence, 300 patients will be randomly assigned to a 6-month treatment in one of three groups of 100 each: oral naltrexone (ON) + depot injectable naltrexone placebo (DINP); oral naltrexone placebo (ONP) + depot injectable naltrexone (DIN); or ONP + DINP. All patients will receive biweekly clinical management/compliance enhancement counseling. Assessments will be done at baseline, at each biweekly appointment during the 6-month of medication treatment, and at 3 and 6 months following the end of the medication. Primary outcome will be the relapse free proportion at months 1-6; secondary outcomes will be time to dropout, opioid positive urines, HIV risk, use of alcohol and other drugs, psychiatric symptoms, and other measures of overall adjustment. We hypothesize that outcomes will be better with DIN than ON, and that each will be more effective than placebo.